1. Biotechnology Industry Organization (BIO) Risk Management Public Workshop Day 1 - April 9, 2003 Risk Assessment in Drug and Biological Development Joanna Haas MD

2. BIO Membership biotechnology companies, academic institutions, state biotechnology centers and related organizations all 50 U.S. states and 33 other nations. health-care, agricultural, industrial and environmental biotechnology products

3. Spectrum of medical products innovative diagnostics and therapeutics serious disorders unmet medical needs orphan and ultra orphan diseases

4. Paradigm for risk assessment empirical approach tailor to each development program shared goal: optimizing benefit risk relation avoid unnecessary delays in access to effective new medicines

5. CASE by CASE approach each proposal is valuable in a specific situations not all are valuable in all cases if used where not applicable –increases uncertainty –increased duration of clinical development –corresponding benefit?

6. From science to new medicines new therapeutic targets new biotherapeutic agents effective risk management strategies –facilitate novel and effective products. –understand risks of novel therapies reap benefits of new knowledge

7. Differential impact young and innovative companies special contribution of -course: same standards of efficacy and safety adjust risk assessment strategy to the needs of the product avoid unnecessary barriers

8. “What is an ideal safety database?” three features of an ideal safety database for “all programs” impact: patients, duration, complexity some features may not be applicable all programs

9. Define an ideal safety database only in the context of a specific program, or type of program

10. Long-term, controlled safety studies theoretical advantages difficulties in practice –patient recruitment and compliance data quality –dropouts and missing data ethical issues in some circumstances alternatives

11. A diverse safety database more representative and generalizable implications for product development. –difficult to demonstrate efficacy confounding factors compliance more patients to demonstrate efficacy - or its absence

12. Diverse database: impact on safety not always better for assessing risk small sub-groups heterogeneous population potential to obscure real safety signals case by case approach

13. Different dose levels clinical development programs –pivotal studies not designed or powered to distinguish between “levels of risk” at different doses additional study arm(s) –more patients, longer duration recruitment in clinical studies –orphan indications

14. Data analysis and presentation creative strategies opportunity to identify and delineate specific safety issues better utilization of data

15. Identification safety issues early prospectively define safety issues “definition of a case” organize and code data clarify distinct safety endpoints tailored to address specific problems facilitates risk management strategy

16. Conclusion BIO looks forward to additional guidance Paradigm: empiric, evidence-based strategies Craft the approach to the problem and setting Goal: innovative, effective and safe biologic products

17. On behalf of BIO: Thank you for the opportunity to address this forum.